MicroRNA-224 Promotes Cell Migration and Invasion by Targeting HOXA5 Expression in Hepatocellular Carcinoma

Abstract Background MicroRNAs(miRNAs) are involved in the regulation of multiple cellular pathways and play a key role in the development and progression of tumor. Multiple studies have shown that abnormal expression of miRNAs has close relation with the incidence of HCC, but the mechanism of miRNAs in HCC still needs further research. Here, we investigated the mechanism of miR-224 in the invasion and metastasis of liver cancer. Methods We employed real-time quantitative PCR to detect the expression of miR-224 and ADAM17 and HOXA5 in HCC tissues. The expression level of HOXA5 in liver cancer tissues was further verified by immunohistochemistry (IHC). Real time PCR and Western bloting were used to detect the expression changes of ADAM17 and HOXA5 caused by overexpression or silencing of miR-224.Dual luciferase reporter assays demonstrated a direct association between miR-224 and its target gene ADAM17 and HOXA5. The migration and invasion experiment, MTT assay and flow cytometry were performed to investigate the changes of the biology function of HCC cell after overexpression or silencing of miR-224. Results The data showed that miR-224 and ADAM17 were significantly up-regulated and HOXA5 was significantly down-regulated in HCC tissues. The targeted regulatory relationship between miR-224 and its target genes ADAM17 and HOXA5 was also demonstrated. More importantly, we found that miR-224 positively regulates cell migration and invasion in HCC, miR-224 overexpression can promote the migration and invasion of BEL-7402 cell, and miR-224 silencing can suppress the migration and invasion of BEL-7402 cell. MiR-224 overexpression can result in the redistribution of cell cycle, the cell percentage of S phase was increased significantly, the cell percentage of G1 phase was decreased significantly, and there is no noticeable change for the cell percentage of G2 phase. Conclusions These results demonstrated that miR-224 may be exert the function of oncogenes in a particular link of cancer cell growth, it will become a promising biological target in the treatment strategy of hepatocellular carcinoma (HCC).